Continuous dopaminergic stimulation in early and advanced Parkinson’s disease

Evidence from preclinical and clinical studies indicates that pulsatile stimulation of striatal dopamine receptors is a key factor in the development of levodopa-associated motor complications. Therefore, in the de novo patient it is believed that providing a more continuous dopaminergic stimulation from the start of antiparkinson therapy may prevent priming for motor fluctuations and dyskinesia. Conversely, in the more advanced patient who is already suffering from motor complications, it is believed that providing a more continuous stimulation may reverse the development of motor complications, enabling the patient to enjoy more stable benefits from therapy. All PD patients eventually require levodopa therapy during the course of their disease, and the benefits of providing continuous dopaminergic stimulation with levodopa have been clearly demonstrated in a number of studies. However, these studies have included the use of approaches such as SC infusion or intra-intestinal infusion. Because these are relatively difficult to handle and not very practical for the patient, compliance is generally low. Therefore, the development of a simple treatment regimen using an oral formulation of levodopa to provide a more continuous dopaminergic stimulation will represent a significant advance in antiparkinsonian pharmacotherapy.